Adult stem cells are multipotent cells capable of executing specific differentiation programs in response to injury or key environmental signals. Many if not all adult organs possess a small number of stem cells, providing the promise of the ability to regenerate organs that are lost through injury or disease. In many tissues, multipotent stem cells are found within specific tissue niches of support cells. These niches contain specific extrinsic and intrinsic cues and act to provide regulatory signals that help pattern tissue self-renewal, proliferation or differentiation. While the relationship between stem cells and niches are known, the controls that regulate the interactions between the cells are an area of active investigation.
The hair follicle is an excellent system to study adult stem cells because of its cycle dependency and relatively short switches between growth and destruction phases. Hair follicles have two parts; one part is a permanent part that has sebaceous glands and the stem cell containing, or bulge, region. The lower or dynamic part goes through genetically controlled cycles of active growth (anagen), destruction phase (catagen) and resting phase (telogen). The timing of each of the cycle phases is exquisitely controlled and varies with environmental controls such as day length and temperature or internal controls such as metabolic or hormone status. During the resting or telogen phase, stem cells are quiescent and remain non-proliferative until the start of the next growth or anagen phase, up to three weeks later in the mouse.
The hair follicle is a complex organ composed of seven differentiation-specific tissue layers including the outer root sheath (ORS), inner root sheath (IRS) and hair shaft (HS). Hair follicle stem cells reside in the bulge region, below the sebaceous gland, in the permanent portion of the hair follicle. It has been proposed that in early anagen phase a signal from dermal papilla activates stem cells in the bulge. This causes proliferation of these cells and subsequently causes downgrowth. As the dermal papilla moves away from the bulge, the stem cells in the bulge return to their quiescent state. Stem cells in the bulge region can also give rise to epidermis in a wounding injury. Investigations over the past decade have elucidated the major signaling regulators controlling the hair cycle, where two of the central pathways for stimulating anagen are the Wnt and Shh pathways.
Hair follicle stem cells are of interest for cosmetic, as well as therapeutic, purposes. For example, androgenic alopecia is the single largest type of recognizable alopecia to affect both men and women, primarily of Caucasian origin. Androgenic alopecia or common baldness represents 99 percent of all cases of hair loss. The condition is characterized by the gradual conversion of terminal hair to short, wispy, colorless vellus hair.
It is generally accepted that genetic hair loss arises from an inherited predisposition activated by circulating androgenic hormones. While many investigators have tried to isolate the causative androgen metabolite, no single molecule has emerged. For example, in comparative studies between non-balding controls, no significant difference between mean hormonal values or amounts has been detected. This suggests that a sensitivity or receptivity to hormones at the cell binding sites within the dermal papilla is a possible factor.
In 1980, the reversal of androgenic alopecia in a male patient receiving minoxidil for hypertension was revealed and minoxidil has since been used to promote hair growth, most commonly by topical application. Minoxidil's vasodilating effect on the scalp is one of the proposed mechanisms by which minoxidil promotes hair growth. However, despite its popularity, minoxidil has not performed in a completely satisfactory fashion in promoting hair growth in all target populations. While minoxidil has been shown to stimulate some hair growth at the apex region of the scalp, hair growth at the frontal region of the scalp, for the most part, has not been shown to be improved by minoxidil treatment alone.
There is a continuing desire to treat hair loss. The present invention addresses this need.